Talking Back to Prozac

By Frederick C. Crews

The Loss of Sadness: How Psychiatry Transformed Normal Sorrow into Depressive Disorder
by Allan V. Horwitz and Jerome C. Wakefield
Oxford University Press, 287 pp., $29.95

Shyness: How Normal Behavior Became a Sickness
by Christopher Lane
Yale University Press, 263 pp., $27.50

Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression
by David Healy
New York University Press, 351 pp., $18.95 (paper)

1.

During the summer of 2002, The Oprah Winfrey Show was graced by a visit from Ricky Williams, the Heisman Trophy holder and running back extraordinaire of the Miami Dolphins. Williams was there to confess that he suffered from painful and chronic shyness. Oprah and her audience were, of course, sympathetic. If Williams, who had been anything but shy on the football field, was in private a wilting violet, how many anonymous citizens would say the same if they could only overcome their inhibition long enough to do so?

To expose one's shyness to what Thoreau once called the broad, flapping American ear would itself count, one might think, as disproof of its actual sway over oneself. But football fans knew that Ricky Williams was no voluble Joe Namath. Nevertheless, there he was before the cameras, evidently risking an anxiety attack for the greater good—namely, the cause of encouraging fellow sufferers from shyness to come out of the closet, seek one another's support, and muster hope that a cure for their disability might soon be found.

Little of what we see on television, however, is quite what it seems. Williams had an incentive—the usual one in our republic, money—for overmastering his bashfulness on that occasion. The pharmaceutical corporation GlaxoSmithKline (GSK), through its public relations firm, Cohn & Wolfe, was paying him a still undisclosed sum, not to tout its antidepressant Paxil but simply to declare, to both Oprah and the press, "I've always been a shy person."

To understand why this was considered a worthwhile outlay, we need to know that the drug makers earn their enormous profits from a very few market-leading products for which new applications are continually sought. If those uses don't turn up through experimentation or serendipity, they can be conjured by means of "condition branding"—that is, coaching the masses to believe that one of their usual if stressful states actually partakes of a disorder requiring medication. A closely related term is more poetical: "astroturfing," or the priming of a faux-grassroots movement from which a spontaneous-looking demand for the company's miracle cure will emanate.

In this instance Cohn & Wolfe, whose other clients have included Coca-Cola, Chevron Texaco, and Taco Bell, was using an athlete to help create a belief that shyness, a common trait that some societies associate with good manners and virtue, constitutes a deplorably neglected illness. Given the altruistic aura of the occasion, it would have been tasteless to have Ricky Williams display a vial of Paxil on the spot. But later (before he was suspended from the football league for ingesting quite different drugs), a GSK press release placed his name beneath this boilerplate declaration:

As someone who has suffered from social anxiety disorder, I am so happy that new treatment options, like Paxil CR, are available today to help people with this condition.

There is nothing out of the ordinary in this episode, but that is just why it bears mentioning. Most of us naively regard mental disturbances, like physical ones, as timeless realities that our doctors address according to up-to-date research, employing medicines whose appropriateness and safety have been tested and approved by a benignly vigilant government. Here, however, we catch a glimpse of a different world in which convictions, perceived needs, and choices regarding health care are manufactured along with the products that will match them.

The corporate giants popularly known as Big Pharma spend annually, worldwide, some $25 billion on marketing, and they employ more Washington lobbyists than there are legislators. Their power, in relation to all of the forces that might oppose their will, is so disproportionately huge that they can dictate how they are to be (lightly) regulated, shape much of the medical research agenda, spin the findings in their favor, conceal incriminating data, co-opt their potential critics, and insidiously colonize both our doctors' minds and our own.

If we hear, for example, that an unprecedented epidemic of depression and anxiety has recently been sweeping the world, we tend not to ask ourselves whose interest is served by that impression. In their painstaking study The Loss of Sadness, Allan V. Horwitz and Jerome C. Wakefield cite the World Health Organization's projection

that by 2020 depression will become the second leading cause of worldwide disability, behind only heart disease, and that depression is already the single leading cause of disability for people in midlife and for women of all ages. The WHO also ranks depression, in its degree of severity for individual victims, ahead of "Down syndrome, deafness, below-the-knee amputation, and angina." But Horwitz and Wakefield cogently argue that those judgments rest on a failure to distinguish properly between major depression, which is indeed devastating for its sufferers, and lesser episodes of sadness. If so, the WHO would appear to have bought Big Pharma's line of goods.

This isn't to say that people who experience infrequent minor depression without long-term dysfunction aren't sick enough to deserve treatment. Of course they are. But as all three of the books under consideration here attest, the pharmaceutical companies haven't so much answered a need as turbocharged it. And because self-reporting is the only means by which nonpsychotic mental ailments come to notice, a wave of induced panic may wildly inflate the epidemiological numbers, which will then drive the funding of public health campaigns to combat the chosen affliction.

This dynamic also applies to a variety of commonplace if bothersome states that the drug makers want us to regard as chemically reparable. They range from excitability and poor concentration to menstrual and menopausal effects and "female sexual dysfunction," whose signature is frustration in bed with the presumably blameless husband or lover. And the same tactic—exaggerate the problem but imply that medication will easily fix it—plays upon legitimate worries over cardiovascular disease, osteoporosis, irritable bowel syndrome, and other threats.[1] As patients on a prophylactic regimen, we are grateful for any risk reduction, however minuscule; but our gratitude leaves us disinclined to ask whether the progressively lowered thresholds for intervention were set without any commercial influence. In that sense our prescribed drugs do extra duty as political sedatives.

2.

Clearly, the drug companies' publicists couldn't exercise their consciousness-shaping wiles so fruitfully without a prior disposition among the populace to strive for self-improvement through every legal means. (Neither GlaxoSmithKline nor Cohn & Wolfe invented The Oprah Winfrey Show.) For the past half-century, first with tranquilizers like Miltown and Valium and more recently with the "selective serotonin reuptake inhibitors" (SSRIs), Americans have required little prodding to believe that a medication can neutralize their social handicaps and supply them with a better personality than the one they were dealt by an inconsiderate fate. The vintage and recent advertisements reproduced in Christopher Lane's polemical Shyness, which features the manipulations that promoted social anxiety disorder to a national emergency, reflect Madison Avenue's grasp of this yearning to be born again without the nuisance of subscribing to a creed.

Hopes along those lines for Valium and its cousins were soon dashed; the drugs did serve as calmants but at the cost of eventually producing mental fogginess and dependency. In the 1990s, however, the SSRIs Prozac, Zoloft, Paxil, Luvox, Celexa, and Efexor seemed very different, enhancing alertness and making many users feel as if a better self were surfacing. Peter Kramer, without ironic intent, named this phenomenon "cosmetic psychopharmacology," and his best-seller Listening to Prozac (1993) swelled a utopian wave that was racing ahead of the drug companies' most optimistic projections.

Even Kramer, though, felt obliged to mention certain troubling effects of Prozac that were already coming to light in the early Nineties. These included, for some users, uncontrollable tremors, diminished sexual capacity, a growing tolerance that was leading to potentially noxious higher doses, and "suicidality," or self-destructive tendencies cropping up in the early weeks of treatment. But because Kramer's readers were weighing the risks not against a discrete medical benefit but against the prospect of becoming self-assured and gregarious at last, those cautions were generally disregarded.

This point is acknowledged in Kramer's recent book Against Depression (2005)—which, however, outdoes even the World Health Organization in its awe before the galloping plague ("The most disabling illness! The costliest!"). Kramer may want to believe the worst about depression's ravages so that the SSRIs he once hailed will still be considered a net boon. Perhaps they are such; I am in no position to judge.[2] But one thing is certain: the antidepressant makers have exploited our gullibility, obfuscated known risks, and treated the victims of their recklessness with contempt. That history needs to be widely known, because the same bullying methods will surely be deployed again as soon as the next family of glamour drugs comes onstream.

Hence the importance of David Healy's stirring firsthand account of the SSRI wars, Let Them Eat Prozac. Healy is a distinguished research and practicing psychiatrist, university professor, frequent expert witness, former secretary of the British Association for Psychopharmacology, and author of three books in the field. Instead of shrinking from commercial involvement, he has consulted for, run clinical trials for, and at times even testified for most of the major drug firms. But when he pressed for answers to awkward questions about side effects, he personally felt Big Pharma's power to bring about a closing of ranks against troublemakers. That experience among others has left him well prepared to puncture any illusions about the companies' benevolence or scruples.

Healy doesn't deny that SSRIs can be effective against mood disorders, and he has prescribed them to his own patients. As a psychopharmacologist, however, he saw from the outset that the drug firms were pushing a simplistic "biobabble" myth whereby depression supposedly results straightforwardly from a shortfall of the neurotransmitter serotonin in the brain. No such causation has been established, and the proposal is no more reasonable than claiming that headaches arise from aspirin deprivation.[3] But by insistently urging this idea upon physicians and the public, Big Pharma widened its net for recruiting patients, who could be counted upon to reason as follows: "I feel bad; I must lack serotonin in my brain; these serotonin-boosting pills will surely do the trick."[4] Thus millions of people who might have needed only counseling were exposed to incompletely explained risks.

Those risks, Healy perceived, included horrific withdrawal symptoms, such as dizziness, anxiety, nightmares, nausea, and constant agitation, that were frightening some users out of ever terminating their regimen—an especially bitter outcome in view of the manufacturers' promise of enhancing self-sufficiency and peace of mind. The key proclaimed advantage of the new serotonin drugs over the early tranquilizers, freedom from dependency, was simply false. Moreover, the companies had to have known they were gambling wildly with public health. As early as 1984, Healy reports, Eli Lilly had in hand the conclusion pronounced by Germany's ministry of health in denying a license to fluoxetine (later Prozac): "Considering the benefit and the risk, we think this preparation totally unsuitable for the treatment of depression."

As for the frequently rocky initial weeks of treatment, a troubling record not just of "suicidality" but of actual suicides and homicides was accumulating in the early 1990s. The drug firms, Healy saw, were distancing themselves from such tragedies by blaming depression itself for major side effects. Handouts for doctors and patients urged them to persist in the face of early emotional turmoil that only proved, they were told, how vigorously the medicine was tackling the ailment. So, too, dependency symptoms during termination were said to be evidence that the long-stifled depression was now reemerging.

The most gripping portions of Let Them Eat Prozac narrate courtroom battles in which Big Pharma's lawyers, parrying negligence suits by the bereaved, took this line of doubletalk to its limit by explaining SSRI-induced stabbings, shootings, and self-hangings by formerly peaceable individuals as manifestations of not-yet-subdued depression. As an expert witness for plaintiffs against SSRI makers in cases involving violent behavior, Healy emphasized that depressives don't commit mayhem. But he also saw that his position would be strengthened if he could cite the results of a drug experiment on undepressed, certifiably normal volunteers. If some of them, too, showed grave disturbance after taking Pfizer's Zoloft—and they did in Healy's test, with long-term consequences that have left him remorseful as well as indignant—then depression was definitively ruled out as the culprit.

Healy suspected that SSRI makers had squirreled away their own awkward findings about drug-provoked derangement in healthy subjects, and he found such evidence after gaining access to Pfizer's clinical trial data on Zoloft. In 2001, however, just when he had begun alerting academic audiences to his forthcoming inquiry, he was abruptly denied a professorship he had already accepted in a distinguished University of Toronto research institute supported by grants from Pfizer. The company hadn't directly intervened; the academics themselves had decided that there was no place on the team for a Zoloft skeptic.

Undeterred, Healy kept exposing the drug attorneys' leading sophistry, which was that a causal link to destructive behavior could be established only through extensive double-blind randomized trials—which, cynically, the firms had no intention of conducting. In any case, such experiments could have found at best a correlation, in a large anonymous group of subjects, between SSRI use and irrational acts; and the meaning of a correlation can be endlessly debated. In contrast, Healy's own study had already isolated Zoloft as the direct source of his undepressed subjects' ominous obsessions.

Thanks partly to Healy's efforts, juries in negligence suits gradually learned to be suspicious of the "randomized trial" shell game. The plaintiffs' lawyers in some of these cases cited his research. But this David doesn't suppose that he has felled Goliath. As he explains, a decisive improvement in the legal climate surrounding SSRIs came only after Eli Lilly bought the marketing rights to a near relative of its own patent-lapsed Prozac. According to the new drug's damning patent application, it was less likely than Prozac to induce "headaches, nervousness, anxiety, insomnia, inner restlessness..., suicidal thoughts and self mutilation" (emphasis added). That disclosure by Prozac's own progenitor neatly illustrates Healy's belief that the full truth about any drug will emerge only when the income it produces has fallen and its defects can be advantageously contrasted with the virtues of a successor product.

Meanwhile, Healy wonders, who will now be sufficiently strong and uncorrupted to keep the drug makers honest? The FDA, he notes, is timid, underfunded, and infiltrated by friends of industry; even the most respected medical journals hesitate to offend their pharmaceutical advertisers; professional conferences are little more than trade fairs; leading professors accept huge sums in return for serving the companies in various venal ways; and, most disgracefully of all, many of their "research" papers are now ghostwritten outright by company-hired hacks. As Healy puts it, Big Pharma doesn't just bend the rules; it buys the rulebook.

3.

There is, however, one rulebook that does place some constraint on what the drug makers can claim. This is the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM). Its four editions (plus interim revisions) thus far from 1952 through 1994 specify the psychological ailments that the whole mental health system has agreed to deem authentic. Although "condition branding" by publicists can make normal people feel like sufferers from a given malady, the malady itself must first be listed in the DSM in order for medical treatments to be approved.

Can we rely on this guidebook, then, for independent, objective judgment about the identification and treatment of mental complaints? The compilers of each edition have boasted that their named disorders rest mainly on research findings, and most physicians take that claim at face value, as do medical insurers, epidemiologists, and the funders of empirical studies. An acquaintance with the DSM's several versions and with the controversies that shaped them, however, suggests that they tell more about the shifting zeitgeist and the factions within the APA than they do about permanently valid syndromes.[5]

Human nature has not metamorphosed several times since 1952, but each DSM has included more disorders than the last. The third edition of 1980 alone, liberally subdividing earlier categories, purported to have unearthed 112 more of them than the second edition of 1968, and by the fourth edition of 1994 there were over 350, marked by such dubiously pathognomonic symptoms as feeling low, worrying, bearing grudges, and smoking. Those stigmata, furthermore, are presented in a user-friendly checklist form that awards equal value to each symptom within a disorder's entry. In Bingo style, for example, a patient who fits five out of the nine listed criteria for depression is tagged with the disorder. It is little wonder, then, that drug makers' advertisements now urge consumers to spot their own defectiveness through reprinted DSM checklists and then to demand correction via the designated pills.

It would be a bad mistake, however, to assume that the shapers of the DSM have been deliberately tilting the manual away from humane psychotherapy and toward biological and pharmaceutical reductionism of the sort exemplified by the serotonin-deficit theory of depression. That very assumption vitiates Christopher Lane's conspiracy-minded book Shyness, which begins plausibly enough as an exposé of the campaign to have shy people view themselves as mentally ill. Unfortunately, Lane couples that theme with a histrionic dismissal of the DSM that is too uncomprehending and partisan to be taken seriously.

Lane is not a psychiatrist but a psychoanalytic literary critic who aligns himself with such empirically insouciant authorities as Jacques Lacan, Elisabeth Roudinesco, and Adam Phillips. Like many another Freudian, he is still in shock over DSM-III of 1980 —the edition that consigned the "neuroses" to limbo, favored descriptive over depth-psychological accounts of disorders, and established the uniform symptom-tallying procedure for certifying a diagnosis.

For Lane, the very attempt to clarify disorders according to their detectable traits constituted a spiteful purging of "almost a century of [psychoanalytic] thought" and thus a reversion to "Victorian psychiatry." He assumes that anyone who hesitates to endorse etiologies based on quarrels between the homuncular ego and superego must be hostile to all mental complexity and hence to psychotherapy in general. That is his charge against DSM-III and DSM-IV. In fact, however, the manual has never stated or implied a preference between talk therapy and pills. If it had done so, it could hardly have served as the consensual guidebook for such a heterogeneous organization as the APA.

In The Loss of Sadness Horwitz and Wakefield discuss the same 1980 change of direction by the DSM that leaves Christopher Lane fuming. As these authors show, the APA leadership's intentions in the late 1970s had nothing to do with pushing drugs and everything to do with lending greater scientific respectability to the psychiatric field. What was wanted thenceforth for the DSM was improved validity and reliability, by virtue of identifying disorders more accurately and providing means of detection that would render several diagnoses of the same patient less divergent.

This remains the DSM's formal goal, however elusive, and it is plainly appropriate and irreversible. What we should really be asking is whether the DSM has approached that goal or merely gestured toward it through the false concreteness of checklists, implying that newly minted disorders are as sharply recognizable as diabetes and tuberculosis. As Horwitz and Wakefield put it, "the reliability might just represent everybody together getting the same wrong answer."

Horwitz and Wakefield's argumentation is as understated as Lane's is melodramatic. Because these collaborators maintain a constructive, scholarly tone and display a total command of the pertinent literature, they will gain a respectful hearing from psychiatrists. Those readers will discover, however, that The Loss of Sadness amounts to a relentless dismantling of the DSM—one that seems confined at first to a single inadequacy, only to blossom into an exposure of the manual's top-to-bottom arbitrariness. I am not sure, in fact, that the authors themselves understand the full gravity of the challenge they have posed for American psychiatry.

At the core of their book lies a demonstration that episodic sadness has always been a socially approved means of adjusting to misfortune and that much is lost, both medically and culturally, when it is misread as a depressive disorder. Yet as Robert L. Spitzer, the chief architect of DSM-III and Christopher Lane's bête noire, concedes in a generous foreword, the manual has propagated that very blunder by failing to clarify the difference between environmentally prompted moods—those responding to stress or hardship—and dysfunctional states persisting long after the causes of stress have abated. In no sense, however, can that indictment be confined to just one disorder. The Loss of Sadness implies that nearly every nonpsychotic complaint is subject to overdiagnosis unless contextual factors— familial, cultural, relational, financial —are weighed in the balance.

As might be expected, then, Horwitz and Wakefield end by begging the compilers of DSM-V (now projected for 2012) to teach their colleagues the need for inquiry into each patient's circumstances before concluding that they are faced with a bona fide disorder. The bar for authentic pathology must be set higher. If this is done, the authors declare, the DSM will be more scientifically respectable; its users, instead of regarding disadvantaged classes as infested with mental illness, will gain an appreciation of socioeconomic reasons for unhappiness; and a brake will be placed on the expensive middle-class hypochondria that the drug companies have so assiduously encouraged and exploited.

All of which would be wonderful, but the scenario is shadowed by Horwitz and Wakefield's own shrewd analysis of the status quo and its beneficiaries. The DSM's laxity about winnowing vague discontents from real maladies is, in financial terms, highly functional for many of its practitioners and their patients. As the product of a guild whose members seek payment for treating whatever complaints are brought to them, the manual must be biased toward overmedicalizing so that both doctors and patients can be served under managed care. As Horwitz and Wakefield themselves observe:

The DSM provides flawed criteria...; the clinician, who cannot be faulted for applying officially sanctioned DSM diagnostic criteria, knowingly or unknowingly misclassifies some normal individuals as disordered; and these two errors lead to the patient receiving desired treatment for which the therapist is reimbursed. What motive would the APA, as a practitioners' union, have for bringing that arrangement to an end? And wouldn't the drug makers, whose power to shape psychiatric opinion should never be discounted, add their weight on the side of continued diagnostic liberality?

Horwitz and Wakefield's admirable concern for scientific rationality points us toward some uncomfortable insights about American psychiatry and its role within a far from rational health care system. That system is too cumbersome and too driven by profit considerations to meet the whole society's medical needs; but citizens possessing full insurance, when they feel mentally troubled in any way, won't be denied medication or therapy or both. Nothing more is required than some hypocrisy all around. As for psychiatry's inability to settle on a discrete list of disorders that can remain impervious to fads and fashions, that is an embarrassment only to clear academic thinkers like these two authors. For bureaucratized psychological treatment, and for the pharmaceutical industry that is now deeply enmeshed in it, confusion has its uses and is likely to persist.

Notes

[1] These matters are discussed in Ray Moynihan and Alan Cassels's Selling Sickness: How the World's Biggest Pharmaceutical Companies Are Turning Us All into Patients (Nation Books, 2005), which also cites the Ricky Williams story.

[2] For recently unearthed considerations bearing on the prudent use of these drugs, see Robert D. Gibbons et al., "Early Evidence on the Effects of Regulators' Suicidality Warnings on SSRI Prescriptions and Suicide in Children and Adults," American Journal of Psychiatry, Vol. 164, No. 9 (September 2007), pp. 1356–1363, and Gonzalo Laje et al., "Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression," American Journal of Psychiatry, Vol. 164, No. 10 (October 2007), pp. 1530– 1538.

[3] The serotonin etiology of depression is concisely disputed in Horwitz and Wakefield's The Loss of Sadness, pp. 168–170. See also Elliot S. Valenstein, Blaming the Brain: The Truth About Drugs and Mental Health (Free Press, 1998), and Joseph Glenmullen, Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Anti-depressants with Safe, Effective Alternatives (Simon and Schuster, 2000).

[4] Healy cites Tipper Gore in 1999: "It was definitely a clinical depression.... What I learned about it is your brain needs a certain amount of serotonin and when you run out of that, it's like running out of gas." Contrary to industry propaganda, the brain possesses no known "depression center," and about 95 percent of our serotonin is found elsewhere in the body. By raising serotonin levels, the SSRIs interfere with production of the other natural "feel-good" chemicals, adrenaline and dopamine. In that sense they are hardly as "selective" as we have been led to believe.

[5] See two important collaborative critiques by Herb Kutchins and Stuart A. Kirk: The Selling of DSM: The Rhetoric of Science in Psychiatry (Aldine de Gruyter, 1992) and Making Us Crazy: DSM: The Psychiatric Bible and the Creation of Mental Disorders (Free Press, 1997).

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